The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease
Year: 2015
Type: review
Study design: Observational Study
Abstract: A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent. These data were combined with those from 28 published data sets by meta-analysis. Furthermore, we tested whether rs75932628 shows association with amyloid beta (Aβ42) and total-tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment. Our data show that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (odds ratio or OR = 2.71, P = 4.67 × 10(-25)). No consistent evidence for association was found between this marker and the risk of FTLD (OR = 2.24, P = .0113 across 2673 cases/9283 controls), PD (OR = 1.36, P = .0767 across 8311 cases/79,938 controls) and ALS (OR = 1.41, P = .198 across 5544 cases/7072 controls). Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF-total-tau (P = .0110) but not Aβ42 suggesting that TREM2's role in AD may involve tau dysfunction.
Source: Alzheimer s & Dementia
Authors: Christina M. Lill, Aina Rengmark, Lasse Pihlstrøm, Isabella Fogh, Aleksey Shatunov, Patrick M. Sleiman, Li‐San Wang, Tian Liu, Christina F. Lassen, Esther Meissner, Panos Alexopoulos, Andrea Calvo, Adriano Chio, Nil Dizdar, Frank Faltraco, Lars Forsgren, Julia Kirchheiner, Alexander Kurz, Jan P. Larsen, Maria Liebsch, Jan Linder, Karen E. Morrison, Hans Nissbrandt, Markus Otto, Jens Pahnke, Amanda Partch, Gabriella Restagno, Dan Rujescu, Cathrin Schnack, Christopher E. Shaw, Pamela J. Shaw, Hayrettin Tumani, Ole‐Bjørn Tysnes, Otto Valladares, Vincenzo Silani, Leonard H. van den Berg, Wouter van Rheenen, Jan H. Veldink, Ulman Lindenberger, Elisabeth Steinhagen‐Thiessen, Stefan Teipel, Robert Perneczky, Hakon Hakonarson, Harald Hampel, Christine A.F. von Arnim, Jørgen H. Olsen, Vivianna M. Van Deerlin, Ammar Al‐Chalabi, Mathias Toft, Beate Ritz, Lars Bertram
Institutions: Max Planck Institute for Molecular Genetics, University of Lübeck, Oslo University Hospital, King's College London, Children's Hospital of Philadelphia, University of Pennsylvania, Max Planck Institute for Human Development, Danish Cancer Society, Technical University of Munich, University of Turin, Linköping University, Goethe University Frankfurt, Umeå University, Universität Ulm, Stavanger University Hospital, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, University of Gothenburg, University of Oslo, Azienda Ospedaliera Citta' della Salute e della Scienza di Torino, Martin Luther University Halle-Wittenberg, University of Sheffield, Haukeland University Hospital, University of Bergen, University of Milan, IRCCS Istituto Auxologico Italiano, University Medical Center Utrecht, Charité – Universitätsmedizin Berlin, German Center for Neurodegenerative Diseases, University of Rostock, West London Mental Health NHS Trust, Imperial College London, Sorbonne Université, Pitié-Salpêtrière Hospital, AXA Research Fund, Institut du Cerveau, Université Pierre-et-Marie-Curie, University of California, Los Angeles
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
Awards: RNA processing proteins and neurodegeneration: exploring mechanisms and modelling disease, Exome sequencing in motor neuron disease: bioinformatic analyses and biological validation of novel variants, Frontotemporal Dementias: Genotypes and Phenotypes, RNA processing proteins and neurodegeneration: exploring mechanisms and modelling disease., Registry Study of Parkinsons Disease in Denmark, STRENGTH, Center of Excellence in Environmental Toxicology
OpenAlex ID: W2055995786